Tissue digestion and cell extraction is a core element of a variety of bioprocessing methods ranging from isolation of the rare cancer stem cell for basic research to the purification of human islets or adipose-derived mesenchymal stem cells for transplant. While procedures vary, it is clear that each tissue digestion procedure subjects the intact tissue to cell stress that can result in a loss of cell viability and function. CPSI-Bioech is focused on improving the bioprocessing of a variety of human cell types at normothermic temperatures (20 to 370C) so that their pharmacological and cell therapy utility can be improved. To this end the Company is developing the CellGuard supplement series - reagents that when added to select bioprocessing procedures will protect and maintain cell viability and function. This, in turn, will lead to fewer post-graft or transfusion problems in the patient. This Phase 1 project proposes to develop CellGuard-TD - a supplement designed to enhance tissue digestion (TD) of human pancreatic tissue for islet isolation (CTDislet). Phase 1 will use a variety of molecular biology methods to develop a prototype CTDislet- the first supplement designed to improve pancreatic islets digestion through cell stress pathway modulation. CTDislet will be based on the well documented apoptosis-prone nature of human pancreatic islets, their low cell yield as a result of warm ischemia exposure, and the collagenase-induced damage to islets that results in a low number obtained from each pancreas. Phase 2 studies will be dedicated to a more in depth analysis and development of CTDislet as well as testing this new formulation at select islets procurement centers. A second aim of the Phase 2 studies will be the development of a "non-synthetic" CTDislet formulation comprised of cell stress inhibitors derived from botanical sources. The intent of this project is to develop a supplement that protects the fragile nature of human pancreatic islets during the isolation and handling process- a technology that will apply to native islets as well as islets differentiated from mesenchymal stem cells and other stem cell sources. The human health consequence of this research will be to improve the isolation, handling and transfusion of human islets used for treating diabetes. PUBLIC HEALTH RELEVANCE: This project is designed to conduct research that will lead to the development of a series of products, termed CellGuard that will protect human cells during manipulation. A variety of human cell types are now being used to treat cancer, diabetes, and also serve as the building blocks of engineered tissues used in the biomedical field. Manipulating human cells such that they can be used for these purposes often compromises both cell function and viability. The CellGuard portfolio of products is designed to protect these cells when they are subjected to these harsh conditions on the path for clinical application. This particular project is designed to develop a CellGuard supplement that will improve the isolation and cell therapy application of human pancreatic islets leading to improved methods for treating diabetes.